结肠炎
炎症
医学
炎症性肠病
胃肠道
免疫学
兴奋剂
受体
药理学
内科学
疾病
作者
Daria Guseva,Katrin Holst,Beate Kaune,Martin Meier,Lydia M. Keubler,Silke Glage,Manuela Büettner,André Bleich,Oliver Pabst,Oliver Bachmann,Evgeni Ponimaskin
出处
期刊:Inflammatory Bowel Diseases
[Oxford University Press]
日期:2014-09-01
卷期号:20 (9): 1516-1529
被引量:58
标识
DOI:10.1097/mib.0000000000000150
摘要
Intestinal inflammation is often associated with an increased level of serotonin (5-HT), an important gastrointestinal signaling molecule involved in gut homeostasis through stimulation of specific receptors. In this study, we investigated the role of 5-HT7 receptor (5-HT7R) in the induction and development of intestinal inflammation using a mouse model of acute and chronic colitis and human patients with Crohn's disease (CD). Acute colitis was induced through administration of dextran sodium sulfate to wild-type, 5-HT7R–deficient mice and hematopoietic bone marrow chimera. Chronic colitis was induced in interleukin 10–deficient mice. The role of 5-HT7R in gut inflammation was assessed using agonist/antagonist treatment. We investigated expression and distribution of 5-HT7R, extent of gut inflammation with magnetic resonance imaging and histological analysis, survival rate, and disease activity index. Finally, biopsies from the large intestine of patients with CD were analyzed. Under basal conditions, 5-HT7R is expressed both in enteric neurons and CD11c+ cells of the large intestine. Expression of 5-HT7R significantly increased after induction of colitis in mice and in inflamed intestinal regions of patients with CD in CD11c/CD86 double-positive cells. Pharmacological blockade or genetic ablation of 5-HT7R resulted in increased severity of both acute and chronic dextran sodium sulfate-induced colitis, whereas receptor stimulation showed an anti-inflammatory effect. Analysis of bone marrow chimera indicated importance of 5-HT7R expressed by hematopoietic cells in intestinal inflammation. The 5-HT7R expressed on CD11c/CD86-positive myeloid cells modulates the severity of intestinal inflammation in an acute and chronic colitis and thus represents a potential therapeutic target for the treatment of inflammatory disorders such as CD.
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